The development and progression of osteoarthrosis, rheumatoid arthritis and ankylosing spondylitis are being determined by means of clinical, radiographic and serological examinations carried out prospectively at two-yearly intervals among adults of the Gila River Indian Community (Pima Indians) in Arizona, in conjunction with epidemiological studies of diabetes in the same community. The purpose of this investigation is to ascertain the determinants of these diseases in the population, and to identify factors which alter the natural history of progression of the disease. Host factors such as age, sex, and various gene markers including HLA and Gm, together with various potential environmental determinants, such as obesity and evidence of exposure to infectious agents, will be studied prospectively to determine their relationship to the development of these diseases. Longitudinal data have now been collected over a 22-year period in the population and represent a unique data set for epidemiological studies of arthritis. The longitudinal data have been used to determine the incidence of rheumatoid arthritis in the population and comparisons have been made with similar data from other ethnic groups and countries. The prognostic significance of rheumatoid factor as a predictive factor for the development of rheumatoid arthritis has been determined. The relationship between the risk of developing rheumatoid arthritis and prognostic significance of rheumatoid factor in relation to HLA-DR typing is being examined.